Advertisement

Grape seed proanthocyanidin extract inhibits interleukin-17-induced interleukin-6 production via MAPK pathway in human pulmonary epithelial cells

  • Hyeongseok Kim
  • Jin Young Kim
  • Hong Suk Song
  • Keon Uk Park
  • Kyo-Chul Mun
  • Eunyoung Ha
ORIGINAL ARTICLE

Abstract

This study was aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on interleukin-17 (IL-17)-induced interleukin-6 (IL-6) production in A549 human pulmonary epithelial cells. Cells were treated with IL-17 (10 ng/ml) or GSPE (50 μg/ml), or both. The effects of GSPE on cell viability and apoptosis were evaluated. The mRNA and protein levels of IL-6 were determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Expressions of inhibitory factor κB-α (IκB-α) and ERK 1/2, p38, and JNK mitogen-activated protein kinase (MAPK) were examined by Western blot analysis. GSPE significantly inhibited both GSPE treatment only and IL-17-induced mRNA expressions and protein productions of IL-6 in pulmonary epithelial cells (p < 0.01). GSPE decreased the IL-17-induced phosphorylation of IκB-α. The IL-17 stimulated ERK 1/2, p38, and JNK MAPK activities and GSPE decreased IL-17-stimulated ERK 1/2, p38, and JNK MAPK activities. GSPE also attenuated TNF-α and IL-1β-induced IL-6 productions (p < 0.05). Our results show that GSPE may inhibit IL-17-stimulated IL-6 productions in human pulmonary epithelial cells by inhibiting MAPK and nuclear factor-κB-mediated signaling pathway.

Keywords

GSPE IL-17 Pulmonary epithelial cells Inflammation IL-6 

Notes

Acknowledgments

The present research has been conducted by attached research institute research grant of Keimyung University in 2007.

References

  1. Akhtar S, Meeran SM, Katiyar N, Katiyar SK (2009) Grape seed proanthocyanidins inhibit the growth of human non-small cell lung cancer xenografts by targeting insulin-like growth factor binding protein-3, tumor cell proliferation, and angiogenic factors. Clin Cancer Res 15:821–831PubMedCrossRefGoogle Scholar
  2. Awane M, Andres PG, Li DJ, Reinecker HC (1999) NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells. J Immunol 162:5337–5344PubMedGoogle Scholar
  3. Bagchi D, Das DK, Engelman RM, Prasad MR, Subramanian R (1990) Polymorphonuclear leucocytes as potential source of free radicals in the ischaemic-reperfused myocardium. Eur Heart J 11:800–813PubMedGoogle Scholar
  4. Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ (1997) Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95:179–189PubMedGoogle Scholar
  5. Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA et al (2000) Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148:187–197PubMedCrossRefGoogle Scholar
  6. Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG et al (2003) Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res 523–524:87–97PubMedGoogle Scholar
  7. Chacon MR, Ceperuelo-Mallafre V, Maymo-Masip E, Mateo-Sanz JM, Arola L, Guitierrez C et al (2009) Grape-seed procyanidins modulate inflammation on human differentiated adipocytes in vitro. Cytokine 47:137–142PubMedCrossRefGoogle Scholar
  8. Cho ML, Heo YJ, Park MK, Oh HJ, Park JS, Woo YJ et al (2009) Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis. Immunol Lett 124:102–110PubMedCrossRefGoogle Scholar
  9. Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, Enelow RI et al (2009) Critical role of IL-17RA in immunopathology of influenza infection. J Immunol 183:5301–5310PubMedCrossRefGoogle Scholar
  10. Hacievliyagil SS, Gunen H, Mutlu LC, Karabulut AB, Temel I (2006) Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease. Respir Med 100:846–854PubMedCrossRefGoogle Scholar
  11. Halliwell B, Gutteridge JM, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119:598–620PubMedGoogle Scholar
  12. Hashimoto T, Akiyama K, Kobayashi N, Mori A (2005) Comparison of IL-17 production by helper T cells among atopic and nonatopic asthmatics and control subjects. Int Arch Allergy Immunol 137(Suppl 1):51–54PubMedCrossRefGoogle Scholar
  13. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producting CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132PubMedCrossRefGoogle Scholar
  14. Johnson-Varghese L, Brodsky N, Bhandari V (2004) Effect of antioxidants on apoptosis and cytokine release in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide. Cytokine 28:10–16PubMedCrossRefGoogle Scholar
  15. Kawaguchi M, Kokubu F, Kuga H, Matsukura S, Hoshino H, Ieki K et al (2001) Modulation of bronchial epithelial cells by IL-17. J Allergy Clin Immunol 108:804–809PubMedCrossRefGoogle Scholar
  16. Kolls JK, Kanaly ST, Ramsay AJ (2003) Interleukin-17: an emerging role in lung inflammation. Am J Respir Cell Mol Biol 28:9–11PubMedCrossRefGoogle Scholar
  17. Laan M, Cui ZH, Hoshino H, Lotvall J, Sjostrand M, Gruenert DC et al (1999) Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. J Immunol 162:2347–2352PubMedGoogle Scholar
  18. Laan M, Lotvall J, Chung KF, Linden A (2001) IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases. Br J Pharmacol 133:200–206PubMedCrossRefGoogle Scholar
  19. Li H, Witte K, August M, Brausch I, Godtel-Armbrust U, Habermeier A et al (2006) Reversal of endothelial nitric oxide synthase uncoupling and up-regulation of endothelial nitric oxide synthase expression lowers blood pressure in hypertensive rats. J Am Coll Cardiol 47:2536–2544PubMedCrossRefGoogle Scholar
  20. Linden A (2001) Role of interleukin-17 and the neutrophil in asthma. Int Arch Allergy Immunol 126:179–184PubMedCrossRefGoogle Scholar
  21. Linden A, Hoshino H, Laan M (2000) Airway neutrophis and interleukin-17. Eur Respir J 15:973–977PubMedCrossRefGoogle Scholar
  22. Linden A, Laan M, Anderson GP (2005) Neutrophils, interleukin-17A and lung disease. Eur Respir J 25:159–172PubMedCrossRefGoogle Scholar
  23. Lippi G, Franchini M, Favaloro EJ, Targher G (2010) Moderate red wine consumption and cardiovascular disease risk: beyond the “French paradox”. Semin Thromb Hemost 36:59–70PubMedCrossRefGoogle Scholar
  24. Liu HT, He JL, Li WM, Yang Z, Wang YX, Yin J et al (2010) Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways. Inflamm Res 59:451–461PubMedCrossRefGoogle Scholar
  25. Ma L, Gao HQ, Li BY, Ma YB, You BA, Zhang FL (2007) Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule expression induced by advanced glycation end products through activation of peroxisome proliferators-activated receptor gamma. J Cardiovasc Pharmacol 49:293–298PubMedCrossRefGoogle Scholar
  26. Ma X, Reynolds SL, Baker BJ, Li X, Benveniste EN, Qin H (2010) IL-17 enhancement of the IL-6 signaling cascade in astrocytes. J Immunol 184:4898–4906PubMedCrossRefGoogle Scholar
  27. Marini M, Vittori E, Hollemborg J, Mattoli S (1992) Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin Immunol 89:1001–1009PubMedCrossRefGoogle Scholar
  28. Miljkovic D, Cvetkovic I, Vuckovic O, Stosic-Grujicic S, Mostarica Stojkovic M, Trajkovic V (2003) The role of interleukin-17 in inducible nitric oxide synthase-mediated nitric oxide production in endothelial cells. Cell Mol Life Sci 60:518–525PubMedCrossRefGoogle Scholar
  29. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N et al (2001) IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108:430–438PubMedCrossRefGoogle Scholar
  30. Ning W, Choi AM, Li C (2005) Carbon monoxide inhibits IL-17-induced IL-6 production through the MAPK pathway in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 289:L268–L273PubMedCrossRefGoogle Scholar
  31. Prause O, Laan M, Lotvall J, Linden A (2003) Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. Eur J Pharmacol 462:193–198PubMedCrossRefGoogle Scholar
  32. Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339:1523–1526PubMedCrossRefGoogle Scholar
  33. Roussel L, Houle F, Chan C, Yao Y, Berube J, Olivenstein R et al (2010) IL-17 promotes p38 MAPK-dependent endothelial activation enhancing neutrophil recruitment to sites of inflammation. J Immunol 184:4531–4537PubMedCrossRefGoogle Scholar
  34. Sen CK, Bagchi D (2001) Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract. Mol Cell Biochem 216:1–7PubMedCrossRefGoogle Scholar
  35. Shalom-Barak T, Quach J, Lotz M (1998) Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem 273:27467–27473PubMedCrossRefGoogle Scholar
  36. Sharma SD, Katiyar SK (2010) Dietary grape seed proanthocyanidins inhibit UVB-induced cyclooxygenase-2 expression and other inflammatory mediators in UVB-exposed skin and skin tumors of SKH-1 hairless mice. Pharm Res 27:1092–1102PubMedCrossRefGoogle Scholar
  37. Sorescu D, Weiss D, Lassegue B, Clempus RE, Szocs K et al (2002) Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105:1429–1435PubMedCrossRefGoogle Scholar
  38. Stankiewicz W, Dabrowski MP, Chcialowski A, Plusa T (2002) Cellular and cytokine immunoregulation in patients with chronic obstructive pulmonary disease and bronchial asthma. Mediat Inflamm 11:307–312CrossRefGoogle Scholar
  39. Starnes T, Robertson MJ, Sledge G, Kelich S, Nakshatri H, Broxmeyer HE et al (2001) Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J Immunol 167:4137–4140PubMedGoogle Scholar
  40. Terra X, Montagut G, Bustos M, Llopiz N, Ardevol A, Blade C et al (2009) Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem 20:210–218PubMedCrossRefGoogle Scholar
  41. Tillie-Leblond I, Pugin J, Marquette CH, Lamblin C, Saulnier F, Brichet A et al (1999) Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus. Am J Respir Crit Care Med 159:487–494PubMedGoogle Scholar
  42. Vanaudenaerde BM, Wuyts WA, Dupont LJ, Van Raemdonck DE, Demedts MM, Verleden GM (2003) Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome. J Heart Lung Transplant 22:1280–1283PubMedCrossRefGoogle Scholar
  43. Wong CK, Ho CY, Li EK, Lam CW (2000) Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus 9:589–593PubMedCrossRefGoogle Scholar
  44. Wong CK, Wang CB, Ip WK, Tian YP, Lam CW (2005) Role of p38 MAPK and NF-kB for chemokine release in coculture of human eosinophils and bronchial epithelial cells. Clin Exp Immunol 139:90–100PubMedCrossRefGoogle Scholar
  45. Wuyts WA, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE, Demedts MG, Verleden GM (2005) Interleukin-17—induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB. J Heart Lung Transplant 24:875–881PubMedCrossRefGoogle Scholar
  46. Yagi Y, Andoh A, Inatomi O, Tsujikawa T, Fujiyama Y (2007) Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts. J Gastroenterol 42:746–753PubMedCrossRefGoogle Scholar
  47. Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J, Shellito JE, Bagby GJ, Nelson S, Charrier K, Peschon JJ, Kolls JK (2001) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194:519–527PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hyeongseok Kim
    • 1
  • Jin Young Kim
    • 2
  • Hong Suk Song
    • 2
  • Keon Uk Park
    • 2
  • Kyo-Chul Mun
    • 1
  • Eunyoung Ha
    • 1
  1. 1.Department of Biochemistry, Pain Research Center, School of MedicineKeimyung UniversityDaeguRepublic of Korea
  2. 2.Department of Internal Medicine and Pain Research Center, School of MedicineKeimyung University Dongsan Medical CenterDaeguRepublic of Korea

Personalised recommendations